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Biomedical subjects

C Richards

Publications and source records attributed to C Richards.

At least 109 records · Page 6Linked to original sources

Development of spontaneous motility in the guppy embryo (Lebistes reticulatus) and the effect of spinal transection.

Guppy (Lebistes reticulatus) embryos pass through a distinct sequence of motor behaviors that leads to swimming capability during the course of their development. We have characterized these activities in order of appearance, with several corresponding morphological features, as belonging to the coil stage, tail-twitch stage, S-movement stage, and swimming stage. A primary feature of development was an increase in the amount of activity per unit of time over these four stages. The developmental pattern of motility was not interrupted by spinal transection until the onset of swimming, implying that supraspinal information is not required for the occurrence of the primitive behaviors that precede swimming. Elimination of swimming by spinal transection did not elicit a reversion to less complex activities, suggesting that once the cerebral control for swimming is developed, it represents a hardwired system not behaviorally reducible to antecedent components.

Animals↗

Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells.

One of the oldest and most preserved of the homeostatic responses of the body to injury is the acute phase protein response associated with inflammation. The liver responds to hormone-like mediators by the increased synthesis of a series of plasma proteins called acute phase reactants. In these studies, we examined the relationship of hepatocyte-stimulating factor derived from peripheral blood monocytes to interferon beta 2 (IFN-beta 2), which has been cloned. Antibodies raised against fibroblast-derived IFN-beta having neutralizing activity against both IFN-beta 1 and -beta 2 inhibited the major hepatocyte-stimulating activity derived from monocytes. Fibroblast-derived mediator elicited the identical stimulated response in human HepG2 cells and primary rat hepatocytes as the monocyte cytokine. Finally, recombinant-derived human B-cell stimulatory factor type 2 (IFN-beta 2) from Escherichia coli induced the synthesis of all major acute phase proteins studied in human hepatoma HepG2 and primary rat hepatocyte cultures. These data demonstrate that monocyte-derived hepatocyte-stimulating factor and IFN-beta 2 share immunological and functional identity and that IFN-beta 2, also known as B-cell stimulatory factor and hybridoma plasmacytoma growth factor, has the hepatocyte as a major physiologic target and thereby is essential in controlling the hepatic acute phase response.

Acute-Phase Proteins↗

Intraspecific cross-protection in mice immunized with irradiated Schistosoma mansoni cercariae.

Several laboratory-maintained strains of Schistosoma mansoni were tested for their relative immunogenicity or susceptibility to anti-schistosome immunity in irradiated cercaria-immunized mice. A total of 11 strains and substrains were used; 7 were of Puerto Rican origin, 3 from Brazil, and 1 from Egypt. Mice were immunized by percutaneous exposure to 50-krad-irradiated cercariae. Immunity was assessed following challenge with cercariae of the homologous or a heterologous strain. The results showed that the choice of either the challenge or immunizing strains was not critical in the development of significant levels of protection. Extensive degrees of cross-protection developed in all intrastrain combinations tested.

Animals↗

Nucleotide sequence of the transposon Tn7 gene encoding an aminoglycoside-modifying enzyme, 3"(9)-O-nucleotidyltransferase.

The nucleotide sequence of a transposon Tn7 DNA fragment encoding a 3"(9)-O-nucleotidyltransferase, an aminoglycoside-modifying enzyme, which mediates bacterial resistance to spectinomycin and streptomycin, was determined. The aadA structural gene was 786 bases long and predicted a polypeptide of 262 amino acids with a calculated molecular weight of 29,207. Comparison of the DNA sequences of Tn7 and plasmid R538-1 indicated that their aadA genes were nearly identical. Comparison of the polypeptides predicted by the aadA genes of Tn7 and Tn554 indicated that the genes were related.

Amino Acid Sequence↗

Mortality, morbidity, and cost-accounting related to coronary artery bypass graft surgery in the elderly.

The purpose of this study was to document early mortality, perioperative complication rate, duration of hospitalization, and costs related to coronary artery bypass graft (CABG) surgery in the elderly. Arbitrarily, elderly patients were defined by age greater than or equal to 65 years; younger patients were less than or equal to 60 years old. A detailed list of specific perioperative complications was analyzed. Early (30-day) mortality was similar between groups, while 120-day mortality was higher among elderly compared with younger patients (7.6% versus 1.3%; p = 0.05). The number of elderly patients with 1 or more complications was also higher than among the younger patients (62% versus 43%; p = 0.05). When the incidences of atrial arrhythmias and transient psychoses were considered minor complications and excluded from consideration, the incidence of major complications was higher in the elderly: 41 major events among 76 younger surviving patients compared with 89 major complications in 61 older surviving patients (p = 0.001). Time spent in the intensive care unit and the duration of postoperative hospitalization were also greater in the elderly (p = 0.01 and p = 0.001, respectively). Finally, the elderly group incurred greater costs than the younger patients (p = 0.03). The likelihood of increased perioperative morbidity in elderly patients is documented in this study. Also, it appears that the increased frequency of complications in elderly patients is associated with a longer hospital stay and greater financial expense. Consequently, the careful preoperative evaluation of these patients, including cautious patient selection, assumes greater importance. After CABG procedures, the highly symptomatic elderly patient may experience dramatic relief of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

In vivo initiation of unstimulated in vitro interleukin-1 release by alveolar macrophages.

Alveolar macrophages (AM) can be stimulated in vitro with material such as lipopolysaccharide, and this activation releases cytokines, collectively called interleukin-1, that can stimulate local cells such as fibroblasts, systemic cells such as lymphocytes, and/or distant parenchymal cells such as hepatocytes. During murine infection with the nematode Nippostrongylus brasiliensis, AM are activated as the parasite larvae migrate through the lung. We examined AM for unstimulated release of lymphocyte-activating factor (LAF) and hepatocyte-stimulating factor (HSF) as evidence of in vivo activation. Two days after infection, marked unstimulated release of LAF was demonstrated along with a smaller increase in unstimulated release of HSF activity. Release of both activities could be further augmented by in vitro stimulation with lipopolysaccharide. Eight days after infection unstimulated HSF activity was even higher than on Day 2, whereas unstimulated LAF release returned to normal. These findings suggest that a natural infective process causes activation of the resident AM population, resulting in release of potent immune and inflammatory-modulating cytokines in situ and that AM play a crucial role in the initiation of host defense and repair responses to infection.

Animals↗

Naloxone administration following brief exposure to novelty reduces activity and rearing in mice upon 24-h retest: a conditioned aversion?

It has recently been reported that naloxone treatment, prior to initial exposure to a novel arena, results in significant behavioural change when animals are retested 24 h later. In an attempt to clarify the nature of this delayed action of the opiate antagonist, three further studies have been performed. In the first experiment, male mice were injected with naloxone hydrochloride (0-10 mg/kg, IP) immediately after their initial experience of the test arena. When retested 24 h later, all groups that had previously received naloxone exhibited greatly reduced activity and rearing, with no evidence of a dose-response relationship. In the second experiment, naloxone (0-10 mg/kg) failed to induce a conditioned place aversion when administered according to the above regimen. In the final experiment, no evidence for a naloxone-induced taste aversion to saccharin was observed. It is concluded that the behavioural changes observed in the open-field study may reflect either (a) subtle aversive properties of naloxone which are insensitive to traditional one-trial paradigms or (b) opioid modulation of memory for non-painful experiences.

Animals↗

Differentiation of schistosomes by species, strain, and sex by using cloned DNA markers.

We have detected species, strain, and sex-specific genetic markers for the genus Schistosoma by Southern blot analysis of its DNA using cloned DNA segments of the Schistosoma mansoni ribosomal gene as probes. Restriction analysis of DNA from eight different strains of S. mansoni, from Africa and the Caribbean, revealed that the predominant or major DNA fragment containing the ribosomal gene unit was the same in each but that low copy number or minor fragments containing the gene varied. It was shown that the detection of these minor fragments could serve as the basis for both strain differentiation and the analysis of individual differences within a strain. Analysis of the parents and progeny of a genetic cross revealed sex-linked markers and suggested that these markers are inherited in a Mendelian fashion. DNAs from the species Schistosoma haematobium and Schistosoma japonicum were also analyzed. Differences in the length of the major repeating unit of the ribosomal gene served to distinguish each species. Furthermore, an array of minor bands was detected in each species, suggesting that strains of S. haematobium and S. japonicum could be differentiated in the same manner as S. mansoni strains.

Animals↗

Depressed mononuclear cell phagocytic activity associated with menstruation.

The peak of the normal distribution curve for pelvic inflammatory disease occurs near the onset of menses. This study was undertaken to determine if there were changes in the cell-mediated immunity of normal menstruating women which could explain the increase in inflammatory disease. The cellular immune response of 8 normal women, measured by number of T- and B-cells and response of mononuclear cells to stimulation with mitogen, was not dependent on the menstrual cycle. However, there was a significant decrease in phagocytic activity of mononuclear cells early in the cycle. The depressed phagocytic activity was not altered by treating the subjects with ibuprofen.

Female↗

The nucleotide sequence of the trimethoprim-resistant dihydrofolate reductase gene harbored by Tn7.

The complete nucleotide sequence of the type I dihydrofolate reductase gene from Tn7 was determined. The structural gene coded for a polypeptide of 157 amino acid residues. The polypeptide deduced from the DNA sequence had a molecular weight of 17,577 which was in good agreement with that estimated by mobility in SDS-polyacrylamide gels. Sequences were identified proximal to the coding region which were similar to those found in the consensus E. coli promoter region and for the initiation of protein synthesis. Features consistent with the termination of RNA transcription were present distal to the structural gene. No homology was apparent when the DNA sequence of the type I gene was compared to the sequence of the type II plasmid DHFR genes, but sequence homology was evident when the type I and E. coli chromosomal enzymes were compared. Homology was greatest in the regions coding for amino acids which in the E. coli chromosomal enzyme are associated with substrate, cofactor and inhibitor binding.

Amino Acid Sequence↗

Fc receptors for IgA and other immunoglobulins on resident and activated alveolar macrophages.

Alveolar macrophage (AMO) were recovered by bronchoalveolar lavage from mice. We have examined the surface of these cells for receptors of immune effector molecules and compared the normal resident AMO to the 'activated' cell present during extensive lung inflammation caused by the parasite Nippostrongylus brasiliensis 2 days after subcutaneous inoculation. As has been shown previously, the resident alveolar macrophage expresses Fc receptors for IgG (90%) and IgE (17%). We now show that a significant proportion of resident AMO possess an Fc receptor for IgA (14%) and this proportion increases to nearly 30% upon activation of the cell, coincident with an increase in release of plasminogen activator and phagocytic activity. This newly described presence of IgA receptors on AMO represents an important demonstration of potential 'arming' of these cells by the predominant antibody in mucous secretions and direct involvement of the AMO in immune mediated reactions in the lung.

Animals↗

The treatment of state I melanoma of the extremities with regional hyperthermic isolation perfusion.

One hundred twenty-two clinically Stage I malignant melanoma patients were treated prospectively in a nonrandomized trial by hyperthermic isolation perfusion with l-phenylalanine mustard (l-Pam), regional lymphadenectomy (RL), and wide local excision (WLE) between April 1965 and July 1980. There were 31 males and 91 females. All primary lesions were retrospectively microstaged by Clark's levels and Breslow's thickness criteria by one of the senior authors. Morphologically, 71% were superficial spreading melanomas (SSM), 16.5% were nodular melanomas (NM), and 11.9% were acral lentiginous melanomas. Survival by microstaging and morphology are reported in Table 1. Eighty-one per cent of all patients were disease-free at five years. Twenty-three patients (18.8%) recurred and of these, 15 died of their disease. This included six of the seven patients with histologically positive lymph nodes. Complications were not only acceptable but preventable and will be discussed. Microstaging provides a valid basis by which to compare treatment regimens and, more importantly, a valid criteria by which to select treatment for a given patient. These data compare favorably with other reported series. At the time these studies were initiated, five-year survivals for clinically Stage I and II melanoma were roughly 55% and 15%, respectively. Existing data clearly indicate that hyperthermic isolation perfusion with RL is superior to WLE and warrants further study in selected patients.

Chemotherapy, Cancer, Regional Perfusion↗

A preliminary study of dynamic muscle function in hereditary ataxia.

Dynamic muscle function was evaluated in nine patients with Friedreich's ataxia (FA) and eight with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The measurement of torque throughout maximum voluntary isokinetic knee movements was used to quantitatively describe muscle weakness in the ataxic patients. Both FA and ARSACS patients were shown to have decreased dynamic strength in comparison to normal values during knee extension and flexion movements at 30 degrees/s. In the FA patients a lower torque-producing capacity was seen in the older patients. The electromyographic (EMG) activity was recorded in lower extremity muscles during the movements. In the vastus lateralis (VL), deviations from the normal EMG activation pattern were described in both groups of patients. A reduced amplitude in the EMG activity in the medial hamstrings (MH) was seen in the majority of the patients. An index of coactivation was defined by comparing the EMG activity when a muscle lengthened (antagonistic) to the EMG activity when the same muscle shortened (agonistic) during the isokinetic contractions. In comparison to normal values increased coactivation indexes were present in the VL and MH in patients of both groups. The characteristics of dynamic muscle strength and the activation of agonistic and antagonistic muscles described in the present study will provide the basis of evaluation for the effects of therapy in these patients.

Adolescent↗

Different types of disturbed motor control in gait of hemiparetic patients.

The pattern of muscle activation in walking was studied in a group of 26 hemiparetic patients. Electromyograms were taken with surface electrodes from 6 muscle groups of the paretic leg and analysed after rectification and time averaging. The sagittal rotations in hip, knee and ankle joint were determined with intermittent light photography. The muscle activation pattern of each patient was compared to that in healthy subjects as well as to the movements performed by the patient and to the normal movement pattern. The normal patterns of movement and muscle activation were assessed from compiled data from 10 healthy female volunteers and average values of angular displacements and amplitude of intergrated EMG were determined at each 5 per cent of the gait cycle. Change of muscle length was determined with a length recording transducer. Gait capacity varied highly in the group of patients studied and the movement pattern also varied markedly. Three types of abnormal muscle activation pattern were disclosed in the patients. In 9 patients, the calf muscles were prematurely activated in the stance phase, probably due to enhanced stretch reflexes (Type I). In another 9 patients, EMG activity was abolished or extremely low in 2 or more of the muscles examined (Type II). In 4 patients, there was a pathological coactivation of several or all of the muscles during part of the gait-cycle, thus disrupting the normal sequential shift of activity in antagonistic muscles (Type III). In the remaining 4 patients, the muscle activation pattern was more complex and no common pattern was discerned.

Adult↗